Doran Mix, BS

CTSI TL1 Predoctoral Training Program

Doran Mix, a fourth-year medical student at the University of Rochester School of Medicine and Dentistry, has had what faculty members are describing as an “exceptional” year-out experience. While conducting research as a CTSI TL1 Predoctoral Program trainee, Mix and his team completed a number of multidisciplinary projects that apply biomedical engineering concepts to solve problems in cardiovascular medicine. Mix says his experience with the CTSI has inspired him to continue to do research for the remainder of his career.

TL1 Predoctoral Training Program

The CTSI’s TL1 Predoctoral Training Program supports students interested in taking a year off from their medical school program to do mentored research in clinical or translational science. Trainees receive a stipend and funding to support research activities. Mix was selected for the program in 2011, between his third and fourth year.

After receiving his bachelor’s degree in computer engineering from the Rochester Institute of Technology, Mix worked has a hardware engineer at InfiMed Inc. (now Varian Medical Systems) in Liverpool, New York,. He enrolled in the University of Rochester School of Medicine and Dentistry in 2008. While attending the Rochester Vascular Symposium during his second year, he met Dr. Ankur Chandra, Assistant Professor of Vascular Surgery and Biomedical Engineering, who gave a presentation about using engineering concepts to improve cardiovascular procedures. That, in addition to Mix’s realization that the vascular system can be mathematically modeled using circuit equations, inspired him to apply his creative engineering ideas to improve vascular surgery outcomes. Dr. Chandra serves as his principle investigator and mentor.

Benefits of the CTSI Year-Out Program

“I think the biggest thing is just to express my gratitude to the CTSI,” Mix said. “It’s every engineer’s dream to have kind of a carte blanche opportunity to apply their ideas.”

Mix says that while working in industry, he was limited by the bottom line. During his year out, however, the CTSI’s support allowed him to collaborate with other researchers and to let his ideas grow, as evidenced by the multiple aims and spinoffs of his original project.

“The opportunities that a year out gives you are absolutely endless, and it’s really exciting to be able to apply your own ideas and try out what it would be like to be a scientist for a year,” he said. “It definitely has empowered me to want to continue research for the remainder of my career.”

The Research

The goal of Mix’s project, entitled “Computer Assisted Surgery Tool for Hemodialysis Fistulas (CAST-HDF),” is to improve the patency of arteriovenous fistulas (AVF) and decrease the rate of associated complications by studying AVF hemodynamics. Mix’s hypothesis is that AVFs tailor-made for individual patients will be more functional and have fewer complications. AVFs – surgically created connections made between an artery and a vein in patients experiencing kidney failure – allow access to the vascular system for hemodialysis.

A fistulagram allows surgeons to determine the anatomy of a patient’s AVF after injecting angiographic dye. Using image processing, surgeons determine the speed at which the dye is traveling. If the width and length of the artery are known, the flow through the vessel can be calculated as well. The pressure and flow at every bifurcation point of the AVF can then be determined using nodal analysis, and the AVF can be designed to meet individual patients’ specific needs.

As part of a spin-off project, Mix and his research team used a hemodynamic simulator (built by students at RIT; see “Collaboration” box) as a novel way to determine the risk at which patients would experience the rupture of an abdominal aortic aneurysm (AAA). While Mix created a 3-D mold of an artificial heart to stress the AAA, RIT student Mallory Wingate (see “Collaboration” box) created 3-D models of patient-specific AAAs from CAT scans. The model AAAs were coated with hydrogel to give them the same mechanical compliance as human vessels. An AAA was then placed in the simulator and a piston squeezed the artificial heart with realistic pulsation, gradually increasing the pressure until the AAA ruptured. The progress to the AAA’s failure can also be modeled using ultrasound strain analysis.

The simulation analysis can help doctors determine whether surgery is necessary. “We can start seeing where the wall is starting to fail, and ultimately, that would give us a way to go back to patients and say, ‘okay, I’m seeing these same conditions just before failure in your aneurysm as I saw in the model on the simulator,’” Mix said. “It’s the proof of concept of an idea I had a long time ago, and it’s realizing it for the first time. It’s pretty cool.”

The Future of the Research

Mix believes his team’s research has the potential to grow into multiple grants. He says studying abdominal aortic strain using ultrasound analysis is low hanging fruit, and that his project adds a level of realism to already existing research. Currently, screening patients for AAAs only involves using default size criteria; Mix’s project, however, studies how the AAA moves under specific patients’ pulsations. Mix says this additional information will easily translate into better clinical decision making – whether or not to operate.

In addition, Mix believes the hemodialysis fistula program is ready to launch into clinical study, which he hopes will happen within the year. He also sees the opportunity for continued collaboration on device design, and collaboration with industry as well.

Collaboration

“I remember Dr. Pearson [Director of the UR Clinical and Translational Science Institute] once saying that the more collaboration we have, the better and more quickly we will get things done,” Mix said.

Mix’s experience proves that point. His project is a multidisciplinary and multi-institutional effort which includes the participation of faculty and students from the University of Rochester and the Rochester Institute of Technology. A central focus of the project – the pulsatile hemodynamic simulator – originally evolved in 2010 from the collaborations of Dr. Karl Schwarz, Director of the Echocardiology Laboratory at the University of Rochester Medical Center; Dr. Daniel Phillips, Director of Biomedical Engineering at RIT; and undergraduate engineering students at RIT completing their senior project. The students designed the simulator, which Mix, Dr. Chandra, and Dr. Steven Day – Assistant Professor of Fluid Mechanics at RIT – later enhanced so it could control contractility.

Mallory Wingate, a second-year biomedical engineering student at RIT, joined Mix’s research team during the summer of 2012 to work on the AAA project. She has firsthand experience with AAAs: her grandfather had an AAA which ruptured and, fortunately, was repaired during emergency surgery.

“Since I saw firsthand what patients who have aneurysms go through, I was really interested in the research they were doing to hopefully provide better care to these patients in the future,” Wingate said.

Joseph Featherall, a post baccalaureate pre-medical student at Columbia University, also joined the research team during the summer of 2012. Featherall was part of the senior project group at RIT that built the simulator.

Spinoffs

Multiple projects have evolved from the original concept using the hemodynamic simulator. RIT PhD candidate Jeff Lillie is designing a microchip that can noninvasively determine a patient’s blood pressure. Using the simulator as a test bed to determine how the different variables in the cardiac cycle affect the system allows the microchip to predict blood pressure.

Geni Giannotti, a third-year biomedical engineering student at RIT, is working with Mix and Dr. Schwarz to study how echo contrast decays under certain hemodynamic conditions, as well as how ultrasound contrast decays because of ultrasonic energy. Ultrasound produces energy and can cause the formation and collapse of bubbles in the blood. By understanding how settings within the ultrasound machine affect bubble decay rates, scientists can develop therapeutic modalities (such as delivering drugs to targeted regions through the bubbles themselves) to improve care.